1,1'-Carbonyldiimidazole → HCID 178501153, compound

HRID 244086Notes

Reaction equation

HRID 244086 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[C:13]([C@H:17]1[CH2:22][CH2:21][C@H:20]([C:23]([OH:25])=O)[CH2:19][CH2:18]1)([O:15][CH3:16])=[O:14].[Cl:26][C:27]1[C:28]([CH:33]([NH2:50])[C:34]2[CH:43]=[C:42]3[C:37]([CH:38]=[CH:39][C:40]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)=[N:41]3)=[CH:36][CH:35]=2)=[N:29][CH:30]=[CH:31][N:32]=1>C1COCC1>[CH3:16][O:15][C:13]([C@H:17]1[CH2:18][CH2:19][C@H:20]([C:23](=[O:25])[NH:50][CH:33]([C:28]2[C:27]([Cl:26])=[N:32][CH:31]=[CH:30][N:29]=2)[C:34]2[CH:43]=[C:42]3[C:37]([CH:38]=[CH:39][C:40]([C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=4)=[N:41]3)=[CH:36][CH:35]=2)[CH2:21][CH2:22]1)=[O:14]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 51051365(3-Chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methanamine2×HCID 178501163HCID 178501163, compound

Product 1

HCID 178501153HCID 178501153, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A THF solution (15 mL) of CDI (1.2 g, 7.3 mmol) and trans-4-carbomethoxycyclohexane-1-carboxylic acid (1.2 g, 6.6 mmol) was stirred at 60° C. for 16 h. The reaction mixture was charged with C-(3-chloropyrazin-2-yl)-C-(2-phenylquinolin-7-yl)-methylamine (compound of Formula IV where Q1=2-phenylquinolin-7-yl) (2.3 g, 6.6 mmol) and stirred at 60° C. for 20 h. The reaction mixture was concentrated in vacuo, taken up in EtOAc, and washed with water (2×) and brine (1×). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (20% EtOAc/Hexanes to 100% EtOAc) the desired product as an orange foam; 1H NMR (CDCl3, 400 MHz) δ 1.48-1.55 (m, 4H), 1.95-2.06 (m, 4H), 2.17-2.24 (m, 1H), 2.26-2.33 (m, 1H), 3.66 (s, 3H), 6.77 (d, 1H, J=7.6 Hz), 7.36-7.41 (m, 1H), 7.45-7.55 (m, 3H), 7.72-7.77 (m, 1H), 7.81-7.89 (m, 2H), 8.11 (d, 2H, J=7.2 Hz), 8.20-8.25 (m, 1H), 8.39 (d, 1H, J=2.4 Hz), 8.60 (d, 1H, J=2.8 Hz); MS (ES+): m/z 515.0 [MH+]; HPLC: tR=3.1 min (Micromass Platform II, nonpolar—5 min).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. washwashed with water (2×) and brine (1×)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by silica gel chromatography (20% EtOAc/Hexanes to 100% EtOAc) the desired product as an orange foam
  7. customHPLC: tR=3.1 min (Micromass Platform II, nonpolar—5 min)

Sources & evidence

ORD record
ord-03d65ec9ef454697951cc99c9aab6322
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

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